2018 |
Bookheimer, Susan Y (co-PI) [⬀] Craske, Michelle G [⬀] Nusslock, Robin Zinbarg, Richard E |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Conproject-001 @ University of California Los Angeles |
0.942 |
2020 — 2021 |
Nusslock, Robin |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Research Project 1: Neuroimmune Mechanisms, Addictive Behaviors, and Cardiometabolic Health Among African American Emerging Adults: a Prospective Study
PROJECT SUMMARY: Research Project 1 The University of Georgia?s (UGA) Center for Translational and Prevention Science (CTAPS; P20 MH068666, P30 DA027827) has been funded continuously since 2003 to advance next-generation basic and preventive investigations of risk, resilience, and drug use among African American young people living in resource poor communities. The CTAPS P50 proposal is based on the hypothesis that progress in the prevention of drug abuse and cardiometabolic disease among African Americans requires consideration of the processes through which chronic, multigenerational poverty and social adversity become embedded in biological and behavioral systems in ways that confer heightened vulnerability to addictive behaviors. Conceptually, the Center?s research program is grounded in a neuroimmune network (NIN) model authored by Center scientists that highlights bidirectional signaling between the brain and immune system in the pathophysiology of addictive behaviors. The NIN model proposes that chronic stressors amplify crosstalk between peripheral inflammation and neural circuitries subserving emotion generation and regulation. This crosstalk results in chronic low-grade inflammation, which upon accessing the brain, accentuates threat processing in cortico-amygdala circuity, attenuates reward processing in cortico-striatal circuity, and dampens prefrontal executive control. NIN dysregulation is hypothesized to predispose individuals to substance misuse and high fat diets, in part, to self- medicate the negative emotions associated with disrupted neural signaling. These behaviors generate additional inflammation, as well as neuroadaptive changes in reward circuitry, further elevating risk for substance misuse. In Research Project (RP) 1, we propose one of the first prospective studies to test NIN predictions from a sample of 225 African American youth. Participants will be ages 18-19 at study enrollment, a period of time in which substance use and unhealthy eating rapidly escalate among African Americans. At Time 1 (T1) and T2 (2.5 years later), participants will complete a blood draw to quantify low-grade inflammation, fMRI scanning of threat-, reward-, and executive control neural activity, and assessments of stress exposure, addictive behaviors, and cardiometabolic risk. RP1 integrates research on multiple organ systems (i.e., brain and immune system) to advance the science of risk and resilience for addictive behaviors and their cardiometabolic health consequences, especially among low income African American communities and other US populations exposed to chronic stress.
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0.948 |
2021 |
Alloy, Lauren Bersh [⬀] Nusslock, Robin |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Integrated Reward-Circadian Rhythm Model of First Onset of Bipolar Spectrum Disorders in Adolescence @ Temple Univ of the Commonwealth
7. Project Summary/Abstract Adolescence is an ?age of risk? for the emergence of first onset of bipolar spectrum disorders (BSD). Despite their prevalence and public health significance, major unanswered questions exist regarding the mechanisms involved in vulnerability to BSDs. BSDs are associated with hypersensitivity to reward and elevated reward- related brain function. However, research has not yet tested whether chronically high reward responsivity (RR) or increases in RR development during adolescence, beyond baseline RR, predicts first onset of BSD. A separate literature documents circadian rhythm disruption in BSDs, and social rhythm disruption (SRD) can trigger BSD episodes. Yet, research has not tested whether baseline circadian dysregulation, chronic social and circadian rhythm disruptions, or increases in these rhythm disruptions during adolescence predict onset of BSD. Further, circadian and reward approaches to BSDs mostly have proceeded in parallel. However, we and others have proposed integrated reward-circadian models of BSDs based on evidence the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. This proposal is the first systematic test of a novel, integrated reward-circadian model for first onset of BSD. We will use an innovative biobehavioral high-risk design to examine bidirectional relationships between multiple indices and domains (monetary, social) of RR and multiple indices of social and circadian rhythms and their joint prediction of first onset of BSD and increases in bipolar symptoms. Three hundred twenty 14-16 year old participants (Ps) will complete a prospective 3-year longitudinal study. Ps with no prior BSD will be selected along the entire dimension of self-reported RR, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1-6, every 6 months, Ps will complete assessments of reward-relevant and SRD life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, Ps also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social RR, and a 7-day EMA period. During each EMA period, Ps will complete continuous measures of sleep/wake and activity (actigraphy) and 3 within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and SRD, monetary and social reward responsivity, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan and DLMO procedure will occur on the day before the start of each EMA period, excluding weekends. This proposal is an innovative integration of research on reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate reward and social/circadian rhythm interventions to treat, and ideally prevent, BSD.
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0.912 |